Regulation of cell proliferation in both normal and tumorous tissue remains of fundamental scientific interest and clinical significance in the prevention and treatment of various types of diseases, particularly cancer and related diseases. In animals, including humans, many of the diseases are recognized as some form of malignant cancer. Plants produce tumor-like growths in response to a variety of stimuli, including certain microorganisms. Because the similarity of animals and plants of basic biological process involved with tumor initiation and growth, materials that affect tumor growth in plants are of more than casual interest in the potential treatment of cancer in humans. Genetic mutations are also recognized as playing significant roles in tumor formation and growth.
In addition to interest in materials that uniquely affect tumor formation in plants, in recent years, clinical and basic interest in potential antitumor properties in animals of a wide range of plant extracts has accelerated dramatically. A significant force in this accelerated interest is recognition of the roles diet plays in both the cause of and prevention of cancer in humans. See, for example, M. B. Sporn, Fed. Proc., 38, 2528 (1979).
Dietary management can significantly affect the risk of developing cancer. Increasingly, plant materials found in common dietary constituents have proved to have antitumor (or anti-cancer) properties. Unfortunately, the opposite is also apparently true, certain plant extracts are known to cause or increase the risk of the development of cancer in humans. Ideally, the human diet should be modified to minimize exposure to dietary carcinogens while simultaneously optimizing intake of cancer preventive agents. Progress towards this condition requires identification of both causative and preventative agents that occur in the human diet.
Plants and plant extracts have long been recognized as having great potential medicinal value. As early as 1500 B.C., The Papyrus Ebers, an ancient Egyptian medical text, recognized over 700 herbal remedies. Records suggest the practice of herbal medicine in Chinese culture as early as 2500 B.C. Native Americans, as cited in numerous sources, effectively used herbals as medicines in addition to related rituals. In first U.S. Pharmacopoeia published in 1820 lists 296 substances, of which 130 were “medicines” used by Native Americans.
The plant kingdom is enormous and diverse and largely unstudied with respect to potential medicinal value. In spite of the historic use of plans and plant extracts, only from 5 to 15% of the 250,000 species of higher plants have been chemically and pharmacologically evaluated for potential medicinal value.
Plant materials, including extracts from various tissues, have been used to treat a variety of conditions and have been recognized as appropriate material for protection under U.S. patent law. For example, U.S. Pat. No. 4,263,286 issued to T. Nakajima, et al. on Apr. 21, 1981 claims a method for treating a wide array of disorders with a soybean (Glycine max L) extract. The '286 patent claims a method of treating consciousness disorders with appropriate doses of phosphatidylcholines (a form of lecithin) with excellent biological activity purified from soy bean plants.
More recently, emphasis has been placed on plant extracts displaying anticarcinogen or cancer chemotherapeutic properties.
U.S. Pat. No. 5,041,425, issued Aug. 20, 1991 to Hasegawa and Lam discloses the use of citrus extracts (limononds) in treating cancer, particularly gastric cancers. The compound reduced induced tumors in mice by 28%, from 100% to 72%. The suggested mode of action was increased antitumor enzymatic activity.
Cancer therapeutic compounds from plants are the subject of other patents. U.S. Pat. No. 6,004,558, titled Method for Treating Cancer with Legume Plant Extracts, issued Dec. 21, 1999 to Thurn and Huang discloses and claims the use of purified extracts of materials derived from various legumes. Tests were conducted on free-cell extracts and on a prostate cancer patient using extracts from legumes from which specific isoflavones (genistein, daidzein, formononetin, and biochanin, and/or their glycosides) were removed. The cell-free tests equate anti-carcinogenic potential in part with reduced cell proliferation, and apoptosis, DNA fragmentation, and growth inhabitation. The efficiency of the extract on prostate cancer was gauged by decreased PSA (prostate specific antigen) level in response to treatment with the extract.
Cyclooxygenase is a metabolic enzyme intermediary involved in stimulating tumor growth. Cancer chemopreventive agents include non-steroid, anti-inflammatory drugs that inhibit cyclooxygenase. Extracts derived from Cassia quinquangulata Rich (Leguminosae) are identified in U.S. Pat. No. 6,008,260, Titled Cancer Chemopreventative Composition and Method issued Dec. 28, 1999 to Pezzuro et. al. The active agent identified in the '260 patent is resveratrol for which the molecular configuration is presented.
The regulation of apoptosis has been associated with anticarcinogens. See, U.S. Pat. No. 5,567,425, title Compositions Which Inhibit Apoptosis, Methods of Purifying the Compositions and Uses Thereof, issued Oct. 22, 1996 to Bathurst et al. The '425 patent discloses materials with apoptosis-regulating abilities derived from plants of at least three families—legumes, nightshade, and garlic. Without reference to antitumor or anticarcinogenic potential, the claims relate to compositions that inhibit normal cell death (antia-apoptic) action. U.S. Pat. No. 6,656,729, with the same title and inventors as the '425 patent which traces to U.S. patent application Ser. No. 08/158,980. Both the '425 and the '729 patents focus on preventing apoptosis using at least one phytogenic inhibitor.
There remains room for detecting and isolating anti-tumor and anti-mutagenic materials in a wider array of taxa of higher plants, for determining the nature of antitumor action, and for characterizing compositions that induce antitumor reactions in tissues.